Hepatitis C (HCV) is the most common cause for chronic liver disease and cirrhosis in the United States, affecting three million U.S residents and causing 8-10 thousand deaths annually. The number of deaths per year due to chronic HCV is projected to triple by 2010-2015, as individual infected during the peak incidence of infection develop end-stage liver cirrhosis. HCV infection is two times mores prevalent in African Americans than White Americans. Furthermore, African Americans appear to have worse outcome, with a higher incidence of primary hepatocellular carcinoma (HCC) and higher death rates due to cirrhosis and HCC. Few African Americans have beer enrolled in clinical trials of HCV therapies. Yet the available data shows significantly lower rates of HCV clearance long-term following interferon alfa (IFN) therapies alone and IFN combined with ribavirin (RBV), compared to White Americans. The lower efficacy of antiviral therapies in African Americans is due, in part, to a higher prevalence of infection with HCV genotype 1 (HCV-1). Yet-the long term clearance of HCV adjusted for HCV genotype is still lower in African American patients, suggesting a potentially important role for host factors in determining the lower treatment response rates. There is a critical need for multicenter clinical trials with adequate numbers of African Americans to conclusively determine the efficacy of combination antiviral therapy for chronic HCV in African Americans and to define the host and viral mechanisms that form the basis for the racial differences in treatment outcomes. Thus, we propose the Baltimore Clinical Center to participate in a multicenter clinical study of resistance to antiviral therapies for chronic HCV-1(VIRAHEP-C). The long-term objective of this award is to identify effective antiviral treatment(s) for African Americans infected with HCV-1. The projects has four Specific Aims: I) Determine the rates of sustained virological response to a 48 week course of combination antiviral therapy, among non-Hispanic, African American and non-Hispanic, White American chronic HCV-1 patients; 2) Determine which host and viral factors predict a sustained virological response to combination antiviral therapy in non-Hispanic, African American and non-Hispanic, White American chronic HCV-I patients; 3) Determine the patterns of HCV (RNA) kinetics in African American and Caucasian chronic. HCV-1 patients during antiviral therapy; 4) Determine whether early HCV (RNA) kinetics accurately predicts the end of treatment and sustained virological responses in African-American and Caucasian chronic HCV-I patients following antiviral therapy. In collaboration with ancillary studies, this project will investigate the influence of selected viral and host factors on the efficacy of treatment for chronic HCV. These studies may provide important new insights into the pathogenesis of HCV and lead to novel therapies for chronic HCV.